The objective of this study is to gain an in depth understanding of demyelinated optic neuritis in humans, from the pathological and pathogenetic viewpoint. Suitable optic neuritis material from humans is rarely available. Since our preliminary study of optic nerves in experimental allergic encephalomyelitis revealed predominantly retrobulbar demyelinating optic neuritis, we propose to develop and use these models. In these studies the disease was in the vicinity where, normally, blood optic nerve barrier is absent indicating the significance of anatomic factors and humoral immune system in development of optic neuritis. Studies of these factors will result in understanding of the pathogenesis of human optic neuritis. Strain-13 guinea pigs will be used to develop acute, chronic and localized retrobulbar optic neuritis. Isologous optic nerve myelin basic protein (BP), in complete Freund's adjuvant, will be used as antigen. Retrobulbar optic neuritis will be produced by subdural injections of lymphocytes sensitized to BP, thru lateral orbitotomy. Antibodies developed against the BP will be isolated for radioimmunoassay, which can be used as a possible diagnostic test in demyelinating optic neuritis in humans. Pathologic materials from human optic neuritis patients will be reviewed at AFIP and findings will be used as a basis for comparison with the experimental lesions. The pathologic changes in the experimental optic neuritis will be sequentially studied by light and by electron microscopy, and the sites of demyelination will be investiggated by the following: (1) autoradiography for disturbances of the axoplasmic flow, (2) horseradish peroxidase for blood-optic nerve barrier alterations, and (3) immunoperoxidase techniques to evaluate the immunologic effects in the blood-optic nerve barrier and demyelination of the optic nerve.